Today there are many people suffering from different types of disorders related to dysfunctions from the respiratory tract. Common examples are bronchitis, chronic bronchitis, chronic obstructive pulmonary disease (COPD), asthma, emphysema, cystic fibrosis (CF) and also common colds. Some of these diseases are chronic conditions and these have large negative impact on the life of the person.
These diseases can be caused by different mechanisms and generally give inflammation. Common to all these disorders are an increased production and accumulation of mucus in the lungs. In the chronic lung diseases the accumulated mucus often becomes colonized by bacteria, further worsening the disease problems.
Different methods of treatment of these disorders have been suggested to treat and/or reduce the symptoms of such disorders. Since most of these disorders are chronic conditions, the method of treatment may be long-term. As these diseases have bacterial colonization as a common denominator, antibiotics are commonly administered. However, in many situations this only lowers the bacterial number for the moment as the mucus remains in the lungs.
Mucus is a mixture of molecules where the large polymer forming mucins are a major constituent. This is MUC2 in the intestine and MUC5B and MUC5AC in the lungs. These molecules are stored in goblet cells and undergo a >1,000-fold expansion upon secretion, a process requiring sufficient amounts of bicarbonate to raise the pH and chelate calcium ions (1). Insufficient amounts of bicarbonate causes the mucus to remain attached to the epithelium in the small intestine as a required enzyme cannot reach its target cleavage site in the mucin (2).
Cystic fibrosis (CF) is caused by a non-functional CFTR chloride and bicarbonate ion channel. However, the coupling between this and the main phenotype with mucus retention and accumulation has remained elusive until recently when we observed that the low amounts of bicarbonate caused by the non-functional CFTR ion channel gave a poor expansion of newly secreted mucin (1). No treatments directly addressing the mucus/mucin abnormality in CF are available, although several treatments like hypertonic saline and mannitol probably affect mucus retention. Most novel therapies for CF are addressing the dysfunctional CFTR channel. These therapies are all dependent on the specific mutation causing disease and are thus individual. No therapies addressing the abnormal mucus for all CF patients are available.
Bronchitis, chronic bronchitis, COPD and asthma are all characterized by mucus retention and accumulation. No major and efficient therapies addressing the stagnant mucus in these diseases are currently available.
Hence, there is a large demand in the art of improved methods and compositions of preventing and treating disorders in relation to dysfunction of the mucus system in the respiratory tract.